We are studying the mechanism of plasmid incompatibility, mainly with the F plasmid of Escherichia coli. This plasmid-controlled function is specific for groups of plasmids and can be used as a criterion for classification of plasmids. For the F plasmid incompatibility exists between integrated F and autonomous F (Fi-Fa incompatibility) and between two autonomous F' factors (Fa-Fa incompatibility). We have obtained a mutant in an integrated F factor which abolishes Fi-Fa incompatibility but not Fa-Fa incompatibility. We have also physically mapped by electron microscope hetero-duplex analysis a short segment on F which contains genes for Fa-Fa incompatibility. We now plan to map precisely the genetic determinants responsible for Fi-Fa incompatibility. We have evidence that Fi-Fa incompatibility is exerted via inhibition of replication of the autonomous F plasmid. For Fa-Fa incompatibility we have no evidence so far for the stage of the plasmid life cycle affected by plasmid incompatibility (replication or segregation). Once we have localized the genes for Fi-Fa incompatibility we shall try to obtain more direct evidence with cell-free systems for the proposed inhibition of plasmid replication. BIBLIOGRAPHIC REFERENCES: Pfister, A., J.K. DeVries and W.K. Maas. Expression of a mutation affecting F incompatibility in the integrated but not the autonomous state of F. J. Bact. 127:348-353 (1976). Palchaudhuri, S. and W.K. Maas. Fusion of two F-prime factors in Escherichia coli studied by electron microscope heteroduplex analysis. Molec. gen. Genet. 146:215-231 (1976).